Feasibility Study Of Laparoscopic-assisted Radical Resection For Rectal Cancer

Colorectal cancer represents a major public health problem. So far, operation is the capital method to treat the colorectal cancer. One of trends in oncological surgery is that less trauma and best function reserved without hurt to the outcome of patients with malignant neoplasms.The application of laparoscopy made it true that more operations trended to minimal trauma. However, the application of laparoscopic operation for the colorectal cancer patients was questioned. The abnormal high port site recurrence rate in early time cast doubt on the safety of laparoscopic operation. With the progress in researches, the different tendency appeared in the application of laparoscopic resection for colorectal cancers. The long-term efficacy of laparoscopic colectomy for colon cancer was authenticated by several prospective randomized controlled trials (RCT). As a result, the laparoscopic operation for colon cancer has been accepted gradually.However, the feasibility of laparoscopic resection for rectal cancer was of general controversies with limited number researches. The questions included: (1) Could laparoscopic operation resect the rectal cancer radically regardless the limitation of narrow pelvic? Would laparoscopic resection increase the complication rate? (2) Did laparoscopic operation for rectal cancer mean minimal trauma? (3) Would laparoscopic operation alter the metastasis pattern of rectal cancer cells? The high rates of anastomotic leakage and circumferential resection margin (CRM) were reported by some researches. As a result, the laparoscopic assisted anterior resection for rectal cancer was not recommended. Most researches evaluating the minimaltrauma value focused the parameters, such as pain, time resuming bowel function and hospital stay, which were the most concerned by the surgeons. The number of research focusing the quality of life was small. The phenomena of more male sexual functional impairments after laparoscopic operation for rectal cancer was reported by a research form UK. There wasn't similar research reported in China. The most of researches focusing the impact of laparoscopic operation on the cancer cell metastasis were in vitro not in vivo. The constituent ratio of rectal cancer of China in colorectal cancer was higher than that of Europe and America. Moreover, 2/3 of rectal cancer lies in the middle and low fragment of rectum. Accordingly, laparoscopic rectal resection made up the major of laparoscopic assisted colorectal cancer operation in China. However, patients with middle-low rectal cancer weren't included in most RCT. Therefore, there weren't enough evidences to support the feasibility of laparoscopic assisted rectal cancer resection. To assess the current situation and feasibility of laparoscopic resection for rectal cancer, four parts researches were designed:Part oneMeta-analysis of short-term efficacy and safety after laparoscopic resectionfor colorectal cancerObjective: To assess the short-term efficacy and safety of laparoscopic resection (LR) for colorectal cancer.Methods: A literature search was performed for the randomized controlled trials (RCT) comparing the difference of laparoscopic and open resection (OR) for colorectal cancer by the end of December 2005. After inclusion and exclusion standard was performed, RCT were appraised by two reviewers independently. The short-term outcomes were extracted and analyzed in Meta analysis.Results: 9RCTs were included in the Meta analysis, which mean quality score was 7.6 ± 0.6. Only 2RCTs aimed the middle-low rectal cancer both with quality score5. The patients' baseline characteristics were similar in two treatment groups. Comparing OR, the incision length in LR deceased 12cm (95%CI[-13.51,-10.49], P<0.01), blood loss deceased 75ml (95%CI[-86.06,-62.99], P<0.01), but the operation time was prolonged 42min (95%CI[32.18,52.50], P<0.01). The length of resected specimens, positive rates of resection margins and number of retrieved lymph nodes didn't show significant differences. There were no significant differences in morbidity rates in operation and post operation between two treatment groups. In patients undergoing LR, the intensity of pain in the first day after operation was shorter (WMD—0.80, 95%CI[-1.26,-0.34], P<0.01), the parenteral narcotics requirement was reduced (SMD=-0.31, 95%CI[-0.42,-0.21], P<0.01), the average time to first flatus, first bowel movement, resuming diet and discharge were reduced (P<0.05).Conclusions: Laparoscopic resection for colorectal cancer is safe and effective, with less pain and faster recovery than open resection. The routine use of laparoscopic assisted resection for colon cancer was supported by enough evidences. However, there was less RCT aimed rectal cancer with low quality score. The role of laparoscopic assisted surgery for rectal cancer will be demonstrated by more RCT.Part two Laparoscopic assisted operation for the cure of rectal cancer: short-term results of three-center case control studyObjective: To assess the short-term efficacy and safety of laparoscopic assisted resection (LR) for rectal cancer.Methods: This is a case control study. The rectal cancer patients' undergone laparoscopic assisted resection came from 3 affiliated hospitals of university between January 2004 and December 2005. The rectal cancer patients adopted open resection (OR) simultaneously were the control. A data collection and comparison was performed which included baseline characteristics of patients, operation, recovery post operation, complication, pathological diagnosis and adjuvant therapy. Follow-upwas ceased by December 2006. Analysis was by intention to treat (ITT).Results: 335 rectal cancer procedures without emergency were performed in 3 centers, which included 115 LR and 220 OR. The patients' baseline characteristics were similar in two treatment groups(P>0.05). 99.4% (333/335) patients didn't receive adjuvant chemoradiotherapy. 85.59% (201/235) patients with anal sphincter preservation received total mesorectal excision. Comparing OR, LR was of shorter incision length, less blood loss, need for transfuse during and post operation and prolonged operation time (P<0.05). 13 (11.3%) patients underwent conversion from laparoscopic to open surgery. There were no differences between 2 operation groups in distance of tumor from the distal section edge, positive rate of length wise section edge, the largest diameter and the number of harvested lymph nodes (P>0.05). The status of circumferential resection margin wasn't reported by any center. There were no differences between 2 operation groups in complication rate during operation, complication rate operation 3months later, reoperation rate in hospital and morbidity rate perioperative (P>0.05). In patients undergoing LR, patient controlled analgesia was less used than OR (13.0%vs34.5%, P=0.000). The parenteral narcotics and oral narcotics requirements didn't show significant differences (P>0.05). Comparing OR, the average time to first flatus, resuming fluid and semifluid diet, defecation, micturition, ground activity and discharge were reduced in LR (P<0.05). The follow-up rate was 93.1% with median 20months (IQR 11months). There were no significant differences between 2 operation groups in rate of adjuvant chemotherapy, regimen composition and complete rate (P>0.05). No statistical differences were found between 2 operation groups in recurrence rate, metastasis rate and overall survival rate (P>0.05).Conclusions: Laparoscopic radical resection for rectal cancer meets the principle of radical operation with fewer traumas, faster recovery and reasonable complication rate. Due to the short-term results, laparoscopic radical resection for rectal cancer was safe and effective. The long-term efficacy will be demonstrated by RCT.Part three Impact of laparoscopic radical resection on quality of life in rectal cancer patientsObjective: To investigate the impact of laparoscopic radical resection on quality of life in rectal cancer patients.Methods: This is a prospective non-randomized observational study. From June 2005 to September 2006, 95 rectal cancer patients joined in the study and accepted radical operation. 42 patients accepted laparoscopic resection (LR), in the same time 53 patients accepted open resection (OR) who was the control. The data of operation and recovery of 2 groups' patients were collected and analyzed. EORTC (European Organization for Research and Treatment) QLQ-C30 and QLQ-CR38 questionnaire were applied to evaluate the scores of quality of life of patients before operation, 1 week later and 3 months later separately. Analysis was by intention to treat.Results: The patients' baseline characteristics were similar in two operation groups(P>0.05). The conversion rate was 23.8% (10/42) in LR. Comparing OR, the operation time was prolonged 40min with shorter incision to 16cm in LR (P<0.05). The time to fist flatus, resuming fluid and semifluid diet and defecation were reduced in LR also(P<0.05). Analysis of QLQ-C30 questionnaire showed that the financial difficulties were always lower in LR than in OR with statistical significance (P<0.05) and clinical significance. Except financial difficulties, only the difference of global health status 1 week later (LR median33.3vsOR median 25.0, P=0.003) and the difference of pain 1 week later (LR median33.3vsOR median 50.0, .P=0.006) were of statistical significance. However, only the latter was of clinical significance. There were no significant differences in most scales between perioperation (P>0.05). Analysis of QLQ-CR38 scores showed that 58.3% (49/84) patients were of micturition problems, 61.1% (11/18) male patients had erection or ejaculation difficulties 3 months later and 4 (4/5) female patients had symptom of dry vagina or pain during intercourse. However, no significant difference was found in any scale ofQLQ-CR38 between LR and OR (P>0.05).Conclusions: Comparing open operation, laparoscopic assisted radical resection for rectal cancer was of fewer traumas and minimal benefit of quality of life. Laparoscopic resection was of no harmful impact on bladder and sexual function of rectal cancer patients.Part four Impact of laparoscopic resection on the copy number of guanylyl cyclase C mRNA in the peripheral blood of rectal cancer patientsObjective: To investigate the impact of laparoscopic resection on circulating free tumor cells in the peripheral blood of rectal cancer patients.Methods: 74 rectal cancer patients without metastasis were recruited. Laparoscopic resection was adopted by 30 patients. Open operation were given to the other 44 patients. Quantitation of peripheral circulating free tumor cells was performed preoperatively, during operation and 1 week later by means of real-time quantitative reverse transcriptase-polymerase chain reaction (Real time RT-PCR) targeting guanylyl cyclase C (GCC) mRNA. 15 healthy volunteer was the control. Moreover quantitation of the subgroup proportion of peripheral blood lymph cell and level of serum C-reactive protein (CRP) were performed preoperatively, 3 day later and 1 week later by means of flow cytometry and nephelometry respectively in rectal cancer patients.Results: GCC mRNA was detected in 52.7%(39/74) preoperative rectal cancer patients with median 485.0copy/ml blood and 13.3%(2/15) healthy control with median 0.0copy/ml blood (P<0.05). There were no significant difference of the GCC mRNA value between 2 operation group at any time(P>0.05). Subgroup analysis showed that the GCC mRNA value during operation and 1 week later were lower than preoperative value in TNM I stage patients undergoing laparoscopic operation(P=0.022). The same trend was found in open operation group without statistical significance(P=0.097). The GCC mRNA during operation was higher thanpreoperative value in N₁ patients undergoing laparoscopic operation(P=0.044), but descend to the preoperative level 1week later. There was not the similar trend in open group(P>0.05). Matching analysis was performed between 13 pairs coming from 2 operation groups targeting the subgroup proportion of peripheral blood lymph cell and serum CRP. Cell immune suppression appeared after operation including the decrease of proportion of T cell, CD4/CD8 ratio and proportion of NK cell. There was no significant difference between 2 operation groups at 3 time points(P>0.05). The CRP degree of 3 day later was higher than that preoperative(P=0.000). The CRP degree of 3 day later was lower in laparoscopic operation group than the value of open operation(P=0.026). With a median follow-up of 9 months(4～16 months), there was no recurrence and death in laparoscopic operation group.Conclusions: Laparoscopic radical resection for rectal cancer had no significantly deleterious effect on circulating free tumor cells with the precondition of no-touch principle. There was less trauma followed laparoscopic operation than open operation. There was no difference in cell immune suppression between the patients having laparoscopic radical resection and those undergone open surgery for rectal cancer.